Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Necrosis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2003

Circulating tumour necrosis factor alpha and soluble tumour necrosis factor receptors in patients with different patterns of rheumatoid synovitis.

OBJECTIVE: To examine the relation between the serum levels of tumour necrosis factor alpha (TNFalpha), soluble tumour necrosis factor receptors (sTNF-R), and the histological pattern of rheumatoid synovitis. METHODS: An enzyme linked immunosorbent assay (ELISA) was used to measure TNFalpha, p55 sTNF-R, and p75 sTNF-R concentrations in the serum of 43 patients with rheumatoid arthritis (RA) and 34 patients with osteoarthritis (OA). RESULTS: Upon histological analysis two variants of rheumatoid synovitis emerged. Twenty six RA specimens presented only diffuse infiltrates of mononuclear cells. In the remaining 17 samples the formation of lymphocytic follicles with germinal centre-like structures was found. Serum concentrations of TNFalpha, p55 and p75 sTNF-R were raised in patients with RA compared with the OA control group (p<0.001 for all comparisons). Levels of TNFalpha, p55 and p75 sTNF-R were higher in the serum of patients with RA with follicular synovitis than in patients with diffuse synovitis (p<0.001, p<0.01, and p<0.05, respectively). Serum concentrations of TNFalpha, p55 and p75 sTNF-R correlated with markers of disease activity. CONCLUSION: Different histological types of rheumatoid synovitis associated with distinct serum levels of TNFalpha and sTNF-R reflect varying clinical activity of the disease and support the concept of RA heterogeneity.

Aged↗
PubMed1970

Renal tubular necrosis and papillary necrosis after gastroenteritis in infants.

Three young infants who had severe gastroenteritis developed radiological and histological features of renal tubular necrosis. Characteristically the excretion urogram showed renal enlargement with prolonged and heavy opacification of the renal parenchyma and a pronounced increase in density of the pyramids. Subsequent radiological studies showed extensive papillary necrosis. Though these infants are now apparently fit, renal damage has occurred and this may eventually give rise to features indistinguishable from chronic pyelonephritis.

Female↗
PubMed2001

Tumor necrosis factor alpha-induced osteoclastogenesis requires tumor necrosis factor receptor-associated factor 6.

Although tumor necrosis factor receptor-associated factor 6 (TRAF6) is required in receptor activator of NF-kappaB-receptor activator of NF-kappaB ligand (RANK-RANKL) signaling for osteoclastogenesis, it has remained unclear whether TRAF6 is crucial in tumor necrosis factor alpha (TNF-alpha)-induced osteoclastogenesis. We examined TRAF6 function in the TNF-alpha-induced osteoclastogenesis by using osteoclast progenitor cells from TRAF6-deficient mice. The results indicated that TNF-alpha did not effectively induce osteoclast differentiation from osteoclast progenitor cells derived from these mice into mature multinucleated osteoclasts, although c-jun N-terminal kinase (JNK) and TNF-alpha activation was observed in osteoclast progenitor cells. Thus, we have provided the first evidence showing that TRAF6 is involved in TNF-alpha-induced osteoclastogenesis.

Animals↗
PubMed2003

CD40 triggering enhances fludarabine-induced apoptosis of chronic lymphocytic leukemia B-cells through autocrine release of tumor necrosis factor-alpha and interferon-gama and tumor necrosis factor receptor-I-II upregulation.

BACKGROUND AND OBJECTIVES: In chronic lymphocytic leukemia (CLL) B-cells are refractory to activation signals and to apoptosis. CD40 triggering, however, rescues CLL B-cells from their anergic state and upregulates the FAS receptor. We therefore studied whether CD40 triggering enhances CLL B-cell sensitivity to fludarabine, and receptors or cytokines potentially involved in apoptosis. DESIGN AND METHODS: CD40-activation of CLL B-cells was carried out by co-culture with CD40L-transfected cells. After fludarabine treatment, apoptosis was evaluated by propidium iodide (PI), annexin-V/PI or DiOC6 staining and flow cytometry analysis. Modulation of Bcl-2, of tumor necrosis factor receptor (TNFRI/II) and release of tumor necrosis factor (TNF)alpha/interferon (IFN)gamma was also analyzed. Furthermore, addition of caspase-inhibitors or anti-TNFalpha/-IFNgamma monoclonal antibodies to fludarabine-treated cells allowed us to determine the mediators of apoptosis. Student's t tests or ANOVA variance statistical analysis were performed to evaluate whether any differences observed might be considered significant. RESULTS: CD40 triggering enhanced fludarabine sensitivity of CLL B-cells, downmodulated Bcl-2 and upregulated TNFRI/II. Caspases 1 and 6 were the major caspases involved in fludarabine apoptosis induction in resting B cells, while only anti-TNFalpha/-IFNgamma monoclonal antibodies reduced apoptosis in activated cells. In agreement with this observation, autocrine production of TNFalpha and IFNgamma by CD40-activated CLL B cells was found. INTERPRETATION AND CONCLUSIONS: B-cells from a considerable proportion of CLL cases studied (11/20) are more prone to fludarabine-induced apoptosis after CD40 triggering; accordingly Bcl-2 expression was lower in activated cells. Moreover, upregulation of TNFRI/II, release of TNFalpha and IFNgamma, and inhibition of apoptosis by anti-TNFalpha/-IFNgamma monoclonal antibodies in CD40-activated cells strongly suggest that these cytokines may play a role in sensitizing B-cells to fludarabine treatment.

Aged↗
PubMed2004

[Potential effect of tumor necrosis factor-alpha and tumor necrosis factor receptor II gene polymorphisms on the pathogenesis of silicosis].

OBJECTIVE: To approach the role of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor receptor II (TNFR II) gene polymorphisms in genetic susceptibility to silicosis and their interaction with silica-dust exposure. METHODS: Two hundred and fifty-nine cases of silicosis and three hundred and forty-one silica-dust exposure workers (control) were selected, and the cases of silicosis were divided into three subgroups based on the various stages of I, II and III. Exposure history, pneumoconiosis history and past history of each subject were obtained by questionnaire. 3 ml peripheral venous blood was drawn from each subject. Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, TNF-alpha and TNFRII gene polymorphisms were analyzed. RESULTS: In both group matching and 1:1 paired matching, there was no significant difference between cases of silicosis and workers in control in distribution frequencies of G/A + A/A (TNF-alpha-308) and T/G + G/G (TNFRII 196) genotypes. The risk of silicosis in those with G/A + A/A genotype was 6.74-fold higher than G/G genotype (OR = 6.74, 95% CI: 1.01 approximately 44.99) in subjects whose exposure time was less than 15 years. CONCLUSION: TNF-alpha and TNFR II gene polymorphisms did not play an important role in susceptibility to silicosis of Han race. There was interaction between polymorphism of TNF-alpha gene promoter and exposure time in the occurrence of silicosis. The risk of silicosis in those with G/A + A/A genotype was significantly higher than G/G genotype in low accumulative exposure.

Adult↗
PubMed1987

Tumor necrosis factor-alpha and hematopoietic progenitors: effects of tumor necrosis factor on the growth of erythroid progenitors CFU-E and BFU-E and the hematopoietic cell lines K562, HL60, and HEL cells.

Macrophages can modulate the growth of hematopoietic progenitors. We have examined the effects of tumor necrosis factor-alpha, a product of activated macrophages, on human erythroid progenitors (CFU-E, BFU-E) and the hematopoietic cell lines K562, HL60, and HEL cells. Tumor necrosis factor (TNF) significantly inhibited CFU-E and BFU-E growth at concentrations as low as 10(-11)-10(-12) M (0.2 U/ml), although erythroid colony and burst formation were not totally ablated. Preincubation of marrow samples with TNF for 15 min was sufficient to suppress erythroid colony and burst formation. Addition of TNF after the start of culture inhibited CFU-E- and BFU-E-derived colony formation if TNF was added within the first 48 h of culture. Additionally, TNF inhibited the growth of highly purified erythroid progenitors harvested from day 5 BFU-E. The colonies which formed in cultures treated with TNF were significantly smaller than those formed in control cultures. TNF (10(-8)-10(-10) M) also suppressed the growth of the hematopoietic cell lines K562, HL60, and HEL cells, with 40%-60% of the cells being sensitive to TNF. Preincubation of HL60 cells with TNF for 15 min significantly inhibited their growth. K562, HL60, and HEL cells expressed high-affinity receptors for TNF in low numbers (6000-10,000 receptors per cell). Fluorescence-activated cell sorter analysis of TNF binding to HEL cells demonstrated that the majority of these cells expressed TNF receptors. These data suggest that: (1) TNF is a rapid irreversible and extremely potent inhibitor of CFU-E, BFU-E, and hematopoietic cell lines K562, HL60, and HEL cells; (2) TNF appears to be acting on a subpopulation of erythroid cells, predominantly CFU-E, BFU-E, and possibly proerythroblasts; (3) TNF appears not to require accessory cells such as lymphocytes or macrophages to inhibit erythroid progenitors; and (4) the presence of TNF receptors on hematopoietic cells is not sufficient to confer sensitivity to TNF since the majority (80%-95%) of HEL cells express TNF receptors while only 40%-60% are inhibited by TNF.

Cell Differentiation↗
PubMed1995

Both tumor necrosis factor receptors, TNFR60 and TNFR80, are involved in signaling endothelial tissue factor expression by juxtacrine tumor necrosis factor alpha.

We have investigated the role of the two distinct tumor necrosis factor (TNF) receptors (TNFR60 and TNFR80) in endothelial cell activation employing an in vitro model of tumor necrosis factor alpha (TNF-alpha)-dependent tissue factor production of human umbilical vein endothelial cells (HUVECs). In this model, tissue factor is produced either on addition of exogeneous TNF-alpha, or by induction of endogenous TNF-alpha via adhesion molecule-linked signal pathways. Under both conditions, tissue factor expression could be partially blocked by antagonistic antibodies against either TNFR60 or TNFR80 and was fully inhibited by simultaneous application of both antibodies. Selective inhibitors of either TNFR60 or TNFR80-induced signal pathways inhibited tissue factor expression, and selective triggering of either of the two TNF receptors by agonistic antibodies induced this response in HUVECs. Furthermore, a coculture system of HUVECs and Chinese hamster ovary transfectants expressing a noncleavable, exclusively membrane-bound form of TNF-alpha resulted in a potent activation of HUVECs with synergistic action of both TNF receptors. Together, these data underline the importance of juxtacrine pathways in endothelial cell activation of procoagulant functions and show that membrane TNF-alpha and both TNFR types play a critical role.

Cell Adhesion Molecules↗
PubMed2002

LIGHT, a member of the tumor necrosis factor ligand superfamily, prevents tumor necrosis factor-alpha-mediated human primary hepatocyte apoptosis, but not Fas-mediated apoptosis.

LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its receptors have been identified as lymphotoxin-beta receptor (LTbetaR) and the herpesvirus entry mediator (HVEM)/ATAR/TR2, both of which lack the cytoplasmic sequence termed the "death domain." The present study has demonstrated that LIGHT inhibits TNFalpha-mediated apoptosis of human primary hepatocytes sensitized by actinomycin D (ActD), but not Fas- or TRAIL-mediated apoptosis. Furthermore, LIGHT does not prevent some cell lines such as HepG2 or HeLa from undergoing ActD/TNFalpha-induced apoptosis. This protective effect requires LIGHT pretreatment at least 3 h prior to ActD sensitization. LIGHT stimulates nuclear factor-kappaB (NF-kappaB)-dependent transcriptional activity in human hepatocytes like TNFalpha. The time course of NF-kappaB activation after LIGHT administration is similar to that of the pretreatment required for the anti-apoptotic effect of LIGHT. LIGHT inhibits caspase-3 processing on the apoptotic protease cascade in TNFalpha-mediated apoptosis but not Fas-mediated apoptosis. In addition, increased caspase-3 and caspase-8 activities in ActD/TNFalpha-treated cells are effectively blocked by LIGHT pretreatment. However, LIGHT does not change the expression of TNFRp55, TNFRp75, and Fas. These results indicate that LIGHT may act as an anti-apoptotic agent against TNFalpha-mediated liver injury by blocking the activation of both caspase-3 and caspase-8.

Antigens, CD↗
PubMed1988

Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum.

Synovial fluids from 6 of 12 patients with rheumatoid arthritis (RA) and from 3 of 11 patients with reactive arthritis contained measurable levels of tumor necrosis factor alpha (TNF alpha). Seven of 12 sera from RA patients contained TNF alpha, while only 1 of those from reactive arthritis patients was positive. Gamma-interferon was detected in the synovial fluids and sera of only the RA patients. Tumor necrosis factor beta was not detected in any sera or synovial fluids. RA patients with detectable TNF alpha had higher erythrocyte sedimentation rates and synovial fluid leukocyte counts.

Adult↗
PubMed1988

Stimulation of the hyaluronic acid levels of human synovial fibroblasts by recombinant human tumor necrosis factor alpha, tumor necrosis factor beta (lymphotoxin), interleukin-1 alpha, and interleukin-1 beta.

Monocyte/macrophage polypeptides (monokines) alter the properties of synovial cells. This interaction could explain some of the properties of the inflamed synovium in rheumatic disease. Only recently has it been possible to test the action of purified monokines on the target synovial cells. We report here that recombinant human tumor necrosis factor alpha, tumor necrosis factor beta (lymphotoxin), interleukin-1 alpha, and interleukin-1 beta stimulate the hyaluronic acid (HA) levels of human synovial fibroblast-like cells. The effect of monokines was generally inhibited by indomethacin, suggesting the involvement of an endogenous cyclooxygenase product in the stimulation, and by the glucocorticoid, dexamethasone. In contrast, all-trans-retinoic acid stimulated synovial cell plasminogen activator activity but did not increase the HA levels. These findings could help to explain the raised HA levels found in the joint fluids and in the circulation of patients with rheumatic disease.

Dexamethasone↗
PubMed1999

Viral coinfection in salmonids: infectious pancreatic necrosis virus interferes with infectious hematopoietic necrosis virus.

Coinfection of farm-reared salmonids involving two viruses has been described, but there is no report on the interactions between viruses. Here we examine whether infectious pancreatic necrosis virus (IPNV) strain Sp interferes with the growth of infectious hematopoietic necrosis virus (IHNV) strain S46, a coinfected isolate from rainbow trout. When BF-2 cell culture was inoculated with S46 the infective titer of the IHNV fraction decreased by 3 log10 units compared to the growth curve of IHNV in the single infection. RT-PCR assay confirmed this reduction, which after successive passages of the co-infected sample led to a decrease in IHNV mRNA and the absence of the specific PCR product for IHNV. Flow cytometry showed that only 13% of the cells inoculated with S46 strain were infected with IHNV at 48-72 h post infection, in contrast to the 50-80% of cells that were positive for IPNV. Exposure of cells to IHNV for 24 h before infection with IPNV did not affect the infective titers of either virus or the PCR results obtained in simultaneous coinfections. Moreover IHNV was not inhibited when the IPNV inoculum was reduced. So, a multiplicity of infection dependence was demonstrated for IPNV-IHNV interference; the RT-PCR assay described here was found to be a suitable technique for identifying and studying dual viral infections.

Animals↗
PubMed1989

Altered macrophage activity and tumor necrosis factor: tumor necrosis and host cachexia.

Tumor necrosis factor (TNF) may be a mediator of cancer cachexia. This study evaluates the activity of macrophages from non-tumor-bearing (NTB) and tumor-bearing (TB) rats by measuring TNF production in response to endotoxin (LPS), both in vitro and in vivo, and correlates macrophage activity with tumor burden and parameters of host cachexia. Isolated macrophages from rats with small tumors, normal food intake, and weight gain secreted more TNF in response to 10 micrograms/ml LPS than macrophages from control NTB rats and behaved similar to activated macrophages from rats previously treated with thioglycollate. Heightened macrophage activity (increased production of TNF in response to LPS) in TB rats increased further as tumor burden increased (r = 0.889, P less than 0.001). Tumor resection reversed the heightened macrophage activity as LPS-induced levels of TNF secreted by macrophages from resected TB rats were not different from those of sham-operated NTB control rats. TB rats had serum levels of TNF activity following an iv bolus of 10 mg/kg LPS greater than those of NTB rats (P less than 0.05). In addition, peak serum TNF activity levels following iv LPS increased directly as tumor burden increased (r = 0.91, P less than 0.001). Supernatants from tissue cultures of the tumor (MCA sarcoma) failed to have any detectable TNF activity. However, large tumors in vivo had increased amounts of necrosis (78 +/- 8%), increased numbers of infiltrating macrophages, and increased levels of TNF (480 +/- 68 U/ml) compared to small tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Increased expression of tumor necrosis factor-alpha converting enzyme and tumor necrosis factor-alpha in peripheral blood mononuclear cells in patients with advanced congestive heart failure.

BACKGROUND: Tumor necrosis factor-alpha converting enzyme (TACE) has recently been identified as a metalloproteinase-disintegrin, which converts pro-tumor necrosis factor-alpha (TNF-alpha) to the mature form, and is an important mediator in the pathogenesis of CHF. AIMS: In order to establish the importance of TACE in the regulation of TNF-alpha synthesis in peripheral blood mononuclear cells (PBMC), we analyzed mRNAs and protein-positive cells of both TACE and TNF-alpha in PBMC obtained from patients with congestive heart failure (CHF). METHODS AND RESULTS: PBMC were obtained from 46 patients with CHF and 22 controls. PBMC were activated by phorbol 12-myristate 13-acetate and ionomycin and assessed for TACE and TNF-alpha mRNAs by real-time RT-PCR, intracellular TACE and TNF-alpha levels by flow cytometry, and TNF-alpha secretion by supernatant ELISA. Levels of TACE and TNF-alpha mRNAs, intracellular TACE and TNF-alpha, and supernatant TNF-alpha were higher in CHF than in controls (P<0.001). There was a positive correlation between TACE and TNF-alpha levels in CHF patients (mRNA: r=0.60, P<0.001, intracellular protein levels: r=0.76, P<0.001). When the CHF group was divided into two subgroups by NYHA functional class (I and II vs. III and IV), levels of TACE and TNF-alpha were significantly higher in severe CHF patients (NYHA III or IV) than in mild CHF patients (NYHA I or II) (mRNA: P<0.001; intracellular protein levels: P<0.001). CONCLUSION: These results demonstrate that in patients with CHF, and especially those with severe CHF, TACE expression in PBMC increases with TNF-alpha expression. These observations suggest that TACE in PBMC is an important regulator of TNF-alpha maturation, meaning that TACE may be a potential target for the inhibition of cellular TNF-alpha production in CHF.

ADAM Proteins↗
PubMed2002

Induction of the hyaluronic acid-binding protein, tumor necrosis factor-stimulated gene-6, in cervical smooth muscle cells by tumor necrosis factor-alpha and prostaglandin E(2).

Immediately before parturition the cervix undergoes striking changes in structure (ripening) that facilitate dilatation and effacement. Cervical ripening shares many features in common with inflammation-associated tissue remodeling, making it a valuable process to explore with respect to the biochemical events in extracellular matrix restructuring. Cervical ripening can be pharmacologically induced with prostaglandin E(2) (PGE(2)). Among the biochemical changes in the cervix at parturition is a marked increase in the hyaluronic acid (HA) content. HA and HA-binding proteins have been implicated in tissue hydration, release of collagenase, and leukocyte migration, but their roles in cervical ripening have not been explored. In the present study we examined the ability of PGE(2) to induce expression of the HA-binding protein, tumor necrosis factor-stimulated gene (TSG)-6, in human cervical smooth muscle cells (hCSMCs) and compared the PGE(2) response to that of tumor necrosis factor-alpha (TNF-alpha), an established inducer of TSG-6. TNF-alpha stimulated TSG-6 mRNA accumulation in a dose- and time-dependent manner, with the maximal response observed at 10 ng/ml after 6 hours of incubation. PGE(2) stimulated TSG-6 mRNA expression, but the magnitude of response was substantially less than that produced by TNF-alpha, and it was maximal only after 24 hours of incubation. Quantitative real-time polymerase chain reaction was performed to assess the induction of TSG-6 mRNA and nascent transcripts at 24 hours of treatment. Induction of TSG-6 mRNA and nascent transcripts in response to 10 micromol/L of PGE(2) was 5.7-fold and 6.3-fold greater than control values, respectively, whereas TNF-alpha (10 ng/ml) induced TSG-6 mRNA and nascent transcripts by 80-fold and 134-fold, respectively. TNF-alpha and PGE(2) stimulated secretion of TSG-6 into the culture medium as detected by Western blotting. The effects of PGE(2) on secretion of TSG-6 were delayed compared to TNF-alpha. A 1.3-kb fragment of the human TSG-6 proximal promoter drove luciferase expression in transfected hCSMCs. PGE(2) increased TSG-6 promoter activity 1.75-fold. Paradoxically, TNF-alpha reduced TSG-6 promoter activity by 50%. We conclude that hCSMCs express the hyaladherin TSG-6; that TSG-6 expression in these cells is regulated by PGE(2) as well as proinflammatory cytokines; responses of hCSMCs to TNF-alpha and PGE(2) are distinct in terms of magnitude and the time course; and PGE(2) and TNF-alpha exert different effects on the TSG-6 proximal promoter.

Cell Adhesion Molecules↗
PubMed1999

Nested PCR improves detection of infectious hematopoietic necrosis virus in cells coinfected with infectious pancreatic necrosis virus.

A nested assay using the reverse transcription-polymerase chain reaction (RT-PCR) was developed for the detection of infectious hematopoietic necrosis virus (IHNV) in cell cultures coinfected with infectious pancreatic necrosis virus (IPNV). Two pairs of primers were designed: one for the amplification of glycoprotein G-specific gene RNA from IHNV (or 1512 bp fragment), and the other for the amplification of an inner 753 bp fragment using the cDNA from the G gene as substrate. Direct RT-PCR was also developed for the amplification of a VP-2 gene fragment from IPNV (613 bp fragment); this method always detected the virus IPNV in the coinfected cells tested but the amplification of IHNV was not as readily achieved. IHNV, however, was detected specifically by nested PCR in coinfected cells at a multiplicity of infection that was 1000 times lower than that of IPNV. Nested PCR was therefore more sensitive than direct RT-PCR for IHNV, and may thus be more appropriate for the detection of low infective titers of IHNV in the presence of IPNV when interference occurs.

Animals↗
PubMed1999

Inducible nitric oxide synthase and tumor necrosis factor in animal models of myocardial necrosis induced by coronary artery ligation or isoproterenol injection.

BACKGROUND: Increased expression of inducible nitric oxide synthase (iNOS) has been described in humans with cardiomyopathies. Most animal models of ischemia-induced heart failure use the surgical ligation of coronary arteries. However, studies of iNOS expression in these models may be confounded by a robust immune response because of the surgical procedure itself leading to iNOS expression in the heart, as well as in other tissues. METHODS AND RESULTS: iNOS expression was studied in adult male rats injected subcutaneously with either 250 mg/kg of isoproterenol (ISO) or vehicle on 2 consecutive days. This approach induces diffuse myocardial necrosis and leads to the development of a dilated cardiomyopathy. Hearts from ISO-injected animals harvested at 6 weeks had evidence of apical and subendocardial scarring. These hearts showed a 9.6-fold (left ventricle [LV], P = .004) and an 11.9-fold (right ventricle, P = .002) increase in the expression of tumor necrosis factor (TNF), and a 6.8-fold increase (LV, P = .0183) in iNOS messenger RNA compared with vehicle-injected controls. iNOS protein also was detectable by immmunoprecipitation in left ventricular muscle from ISO-injected animals, as well as by immunohistochemical analysis. CONCLUSION: Expression of TNF and iNOS in the heart is increased in an experimental model of dilated cardiomyopathy that minimizes the confounding effects of surgery, supporting a role for the activation of innate immunity signaling pathways in the pathogenesis of heart failure.

Animals↗
PubMed1988

Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice.

We find a strong synergism between tumor necrosis factor (TNF) and bacteria or their products. Endotoxin-"free" recombinant TNF, even at very high doses (160 micrograms), did not alone cause hemorrhagic necrosis (HN) in the skin of normal mice. Similarly, TNF alone had a low systemic toxicity in tumor- and pathogen-free mice. However, TNF given intravenously with nanogram quantities of the endotoxin lipopolysaccharide caused lethal shock. Furthermore, subcutaneous injection of lipopolysaccharide made skin susceptible to subsequent induction of HN by TNF injected in the same site 24 hr later. Mycoplasma-infected cells or corynebacteria also synergized with TNF to cause HN or lethal shock. In addition, we find that lymphotoxin, a cytokine functionally and genetically related to TNF, also synergized with the bacteria to cause HN, whereas interleukin 1 alpha or interferon gamma did not. Together, the results indicate that a synergy between TNF and bacteria or their products causes HN and lethal shock in normal mice.

Animals↗
PubMed1984

Selective necrosis and total necrosis in focal cerebral ischemia. Neuropathologic observations on experimental middle cerebral artery occlusion in the macaque monkey.

Temporary (15 minutes to 24 hours) or permanent focal cerebral ischemia was induced in 87 awake monkeys (Macaca mulatta and Macaca fasicularis) by transorbital snare ligation of the middle cerebral artery (MCA) and neuropathological evaluation was carried out two weeks later. The size, location and histology of lesions varied within each time-period of MCA occlusion. However, most animals that underwent long-term ischemia (eight hours to permanent) had a single, confluent infarct involving deep and sometimes cortical structures. These animals had total necrosis chracterized by: 1. indiscriminate involvement of white and gray matter, 2. relatively sharp margins containing astrocytic and mononuclear cells, 3. an inner zone of liquefaction, infiltrated with fat-laden macrophages and newly formed blood vessels. Animals that underwent moderate to short-term ischemia (30 minutes to four hours) showed multiple, non-confluent deep infarcts. These animals had selective necrosis characterized by: 1. involvement of gray matter and relative sparing of white matter, 2. poorly circumscribed, multiple and often perivascular lesions with incomplete tissue destruction, 3. preferential loss of neurons and proliferation of reactive astrocytes and microglia.

Animals↗